We have previously demonstrated that the forearm vasculature of hypertensive patients is less responsive to the effects of infused acetylcholine (Ach) which causes the endothelium to release endothelium-- derived-relaxant factor (EDRF). In this study, we investigated the effect of Ach on the endothelium lining of coronary conductance and resistance vessels in patients with various chest pain syndromes. The effects of intracoronary Ach on epicardial coronary diameter, flow and coronary resistance in 16 pts with normal epicardial coronary arteries and chest pain, and those with normal epicardial coronary arteries and hypertrophic cardiomyopathy were studied. Epicardial coronary artery diameter did not change significantly. However, GCV flow increased and coronary vascular resistance decreased incrementally to Ach. At 10-8 molar dose of Ach, GCV flog increased by 12+3%; at 10-7 molar, GCV flow increased by 34+6%; at 10-6 molar dose, it increased by 49+9%. compared to baseline. This suggests that endothelium-dependent dilation of coronary resistance vessels occurs independent of epicardial coronary artery changes. Thus, it is conceivable that the endothelium may regulate coronary resistance and flow in man. It remains to be determined whether abnormalities of vasodilatation of resistance vessels my be secondary to endothelial dysfunction, and thus contribute to myocardial ischemic syndromes in some pts.